This invention relates generally to methods of performing spectral analysis in a pharmaceutical dissolution process, and more particularly to such methods using fiber optic probes.
Dissolution monitoring is used to determine the concentration of a pharmaceutical active ingredient as a function of time. Dissolution testing is an FDA requirement and an important step in the drug development process. A tablet, for example, is dropped into a temperature-controlled reservoir containing an aqueous solution. The concentration of the active ingredient in solution is measured as the tablet dissolves. The concentration can be determined through an optical spectroscopic measurement, primarily in the ultraviolet to visible portion of the spectrum. The sample is either removed from the reservoir for measurement or an in situ measurement probe is inserted into the reservoir.
In situ measurements offer increased measurement efficiency, while potentially reducing measurement errors due to extraction. In situ probes use fiber optic coupling to connect the measurement probe to both the light source and the detecting spectrometer.
Dissolution testing is usually performed automatically using apparatus designed to sample continuously or discretely from dissolution vessels. In a continuous sampling procedure, a single fiber optic probe per dissolution vessel is employed. In a discrete sampling procedure, a fiber optic probe is used for sampling in a plurality of dissolution vessels. A robot arm dips the probe in a first dissolution vessel where optic measurements are made to measure certain properties of a dissolution solution in the dissolution vessel. The robot arm then moves the probe from the first dissolution solution to a bath where the probe is cleaned, and then dips the probe into a second dissolution vessel for measuring certain properties of a second dissolution solution.
A disadvantage of prior art probes used in dissolution testing is that air occasionally becomes trapped in a sampling region of the probe (e.g., adjacent a lens or window). The trapped air impedes accurate spectral analysis of the dissolution solution.
Among the objects and advantages of the present invention may be noted the provision of an improved method for performing spectral analysis in a pharmaceutical dissolution process; and the provision of such a method employing a fiber optic probe which minimizes entrapment of air within the probe sample region.
Generally, a method of the present invention is for performing spectral analysis in a pharmaceutical dissolution process. The method comprises inserting a fiber optic probe of a spectral analyzer into a dissolution vessel. The dissolution vessel contains a dissolution medium. The probe has a launch cable, a return cable, a launch lens portion, a return lens portion and a reflector. The cables, lens portions and reflector are arranged and adapted to form a light pathway whereby light transmitted through the launch cable passes through the launch lens portion, through a volume of the dissolution media in the spacing between the launch lens portions and the reflector, then through the return cable. The spacing between the reflector and the lens portions comprise a sample region. The fiber optic probe is sized and adapted to prevent bubbles in the dissolution media from being trapped in the sample region. The method further comprises transmitting light along the optic pathway, and analyzing the transmitted light for determining certain optical properties of the dissolution media in the sample region.
Another aspect of the present invention is a method of making a fiber optic probe. The method comprises placing into a sheath a launch cable, a return cable, a launch lens portion, a return lens portion, and a reflector. The launch lens portion is forward of and aligned with the launch cable. The return lens portion is forward of and aligned with the return cable. The launch lens portion has a focal length substantially equal to the focal length of the return lens portion. The sheath has an end margin extending forward from the lens portions and terminating in a sheath end. The end margin of the sheath has at least one slot therein. The method further comprises: positioning a reflector element adjacent the sheath end and spaced from the lens portions by the desired sample region length; placing the return cable into optical communication with an optical detector; transmitting light along the launch cable through the launch lens portion and to the reflector element; adjusting the position of the reflector element relative to the sheath to substantially maximize detection by the detector of the transmitted light reflected from the reflector through the return lens portion and through the return cable and to the detector; and securing the reflector element to the sheath to maintain the reflector element in its adjusted position.
Other objects and features will be in part apparent and in part pointed out herinafter.